Field of the Invention
The present invention relates to novel antibacterial compounds referred to herein generally as a thermal isomer of difficidin and thermal isomer of oxydifficidin. Also disclosed is process for preparing, isolating, and purifying said compounds. As employed herein, the term "thermal isomer of difficidin" refers to the compound (Z,Z,E,Z,Z,)-16-dihydroxyphosphinoxy-5,7-dimethyl-4-methylene-22-((E)-3-me thyl-3,5-hexadienyl)oxacyclo-docosa-8,10,12,17,19-pentaen-2-one, which has the structural formula as described in Formula II, hereinbelow, wherein R.sup.1 is hydrogen, and R.sub.a and R.sub.b have the recited meanings, thus affording various salt forms thereof. Corresponding, the term "thermal isomer of oxydifficidin", as used herein, refers to the compound (Z,Z,E,Z,Z,)-16-dihydroxy-phosphinoxy-5,7-dimethyl-6-hydroxy-4-methylene-2 2-((E)-3-methyl-3,5-hexadienyl)oxacyclodocosa-8,10,12,17,19-pentaen-2-one, which has the structural formula as described in Formula II, hereinbelow, wherein R.sup.1 is hydroxy, and R.sub.a and R.sub.b have the indicated meanings. The novel antibacterial compounds can be obtained by microbiological cultivation of Bacillus subtilis, MB 3575 or MB 4488 deposited with the American Type Culture Collection, Rockville, Md. under the designations ATCC 39374 and 39320, respectively.
The noval antibacterial compounds of the present invention are broad spectrum antibacterials with good potency against aerobic microorganisms and exceptional potency against anaerobic microorganisms. They also exhibit good in vitro activity against microorganisms that have developed resistance to conventional antibacterials. They may be used parenterally in the treatment of gram positive and gram negative bacterial infections.